The long-term objective of this project is to understand the interactions between the spinal cord and the brainstem in the control of vertebrate locomotion. This project will focus on the interactions of ascending spinal neurons with the descending reticulospinal neurons in the lamprey, a lower vertebrate. The lamprey is used because the brainstem/spinal cord networks in lamprey are simpler and more direct than the comparable networks in higher vertebrates. During locomotor activity in lamprey, the reticulospinal neurons receive rhythmic locomotor signals directly from the ascending spinal neurons, and stimulation of reticulospinal neurons produces coordinated motor patterns in the spinal cord called locomotor output synergies. The overall hypothesis of the project is that ascending spinal neurons provide feedback signals about specific spinal network subsets to reticulospinal cells that in turn produce particular locomotor output synergies. This hypothesis will be addressed using intracellular recording of membrane potential of these cells in the isolated brainstem/spinal cord preparation of the lamprey. The specific aims of the study will address the following questions regarding the overall hypothesis: 1) Does each reticulospinal cell produce a particular locomotor output synergy that is a consistent characteristic of that cell? 2) Does the reticulospinal cell stimulation pattern alter locomotor output synergies? 3) Does the timing of rhythmic activity in each reticulospinal cell correlate with its locomotor output synergy? 4) Do the synaptic inputs that underlie reticulospinal neuron rhythmic activity correlate between pairs of cells according to their locomotor output synergies? 5) Do individual spinobulbar neurons represent the activity of particular spinal network subsets? This research is relevant to public health because in humans, as in all vertebrates, the accurate production of locomotor movements requires that the brain exert precise control of the spinal cord where the locomotor neural networks reside. For precise control of these locomotor networks, the brain must be kept informed about the activity of the spinal cord. Therefore, understanding the mechanisms underlying the interactions between spinal cord and the brain in the control of locomotion is important for the development of effective therapeutic measures for treating human disorders of motor control and locomotion.